CN116270901B - Chinese herbal compound and pharmaceutical composition thereof - Google Patents
Chinese herbal compound and pharmaceutical composition thereof Download PDFInfo
- Publication number
- CN116270901B CN116270901B CN202211675138.2A CN202211675138A CN116270901B CN 116270901 B CN116270901 B CN 116270901B CN 202211675138 A CN202211675138 A CN 202211675138A CN 116270901 B CN116270901 B CN 116270901B
- Authority
- CN
- China
- Prior art keywords
- group
- mice
- pharmaceutical composition
- longan
- blood
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 title abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 45
- 240000001008 Dimocarpus longan Species 0.000 claims abstract description 14
- 235000000235 Euphoria longan Nutrition 0.000 claims abstract description 14
- 240000005373 Panax quinquefolius Species 0.000 claims abstract description 12
- 235000003140 Panax quinquefolius Nutrition 0.000 claims abstract description 12
- 240000007164 Salvia officinalis Species 0.000 claims abstract description 12
- 241000305491 Gastrodia elata Species 0.000 claims abstract description 9
- 244000131316 Panax pseudoginseng Species 0.000 claims abstract description 9
- 235000003181 Panax pseudoginseng Nutrition 0.000 claims abstract description 9
- 235000017276 Salvia Nutrition 0.000 claims abstract description 4
- 229940079593 drug Drugs 0.000 claims description 20
- 239000000843 powder Substances 0.000 claims description 10
- 235000005412 red sage Nutrition 0.000 claims description 8
- 241000305492 Gastrodia Species 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000006187 pill Substances 0.000 claims description 5
- 239000003826 tablet Substances 0.000 claims description 5
- 241000180649 Panax notoginseng Species 0.000 claims description 4
- 235000003143 Panax notoginseng Nutrition 0.000 claims description 4
- 239000000872 buffer Substances 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 230000003920 cognitive function Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 239000002250 absorbent Substances 0.000 claims description 2
- 230000002745 absorbent Effects 0.000 claims description 2
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000006184 cosolvent Substances 0.000 claims description 2
- 239000003431 cross linking reagent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000002270 dispersing agent Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 239000012675 alcoholic extract Substances 0.000 claims 1
- 239000006286 aqueous extract Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 abstract description 23
- 239000008280 blood Substances 0.000 abstract description 23
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 abstract description 7
- 208000002173 dizziness Diseases 0.000 abstract description 7
- 206010022437 insomnia Diseases 0.000 abstract description 7
- 208000009205 Tinnitus Diseases 0.000 abstract description 6
- 231100000886 tinnitus Toxicity 0.000 abstract description 6
- 230000007812 deficiency Effects 0.000 abstract description 5
- 208000000044 Amnesia Diseases 0.000 abstract description 3
- 208000031091 Amnestic disease Diseases 0.000 abstract description 3
- 206010012289 Dementia Diseases 0.000 abstract description 3
- 208000000059 Dyspnea Diseases 0.000 abstract description 3
- 206010013975 Dyspnoeas Diseases 0.000 abstract description 3
- 206010062717 Increased upper airway secretion Diseases 0.000 abstract description 3
- 206010071299 Slow speech Diseases 0.000 abstract description 3
- 206010047513 Vision blurred Diseases 0.000 abstract description 3
- 238000009825 accumulation Methods 0.000 abstract description 3
- 230000006986 amnesia Effects 0.000 abstract description 3
- 208000026435 phlegm Diseases 0.000 abstract description 3
- 208000013220 shortness of breath Diseases 0.000 abstract description 3
- 206010014080 Ecchymosis Diseases 0.000 abstract 1
- 208000006083 Hypokinesia Diseases 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 77
- 238000002474 experimental method Methods 0.000 description 40
- 241000699666 Mus <mouse, genus> Species 0.000 description 27
- 210000001519 tissue Anatomy 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000012360 testing method Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 230000002269 spontaneous effect Effects 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- 238000001514 detection method Methods 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 230000003542 behavioural effect Effects 0.000 description 11
- 238000010175 APPswe/PSEN1dE9 Methods 0.000 description 10
- 239000001993 wax Substances 0.000 description 10
- 210000001320 hippocampus Anatomy 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 230000001149 cognitive effect Effects 0.000 description 8
- 230000000971 hippocampal effect Effects 0.000 description 8
- 230000015654 memory Effects 0.000 description 8
- 239000008096 xylene Substances 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 230000018044 dehydration Effects 0.000 description 7
- 238000006297 dehydration reaction Methods 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 239000002504 physiological saline solution Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000012347 Morris Water Maze Methods 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000010171 animal model Methods 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 5
- 238000005286 illumination Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012188 paraffin wax Substances 0.000 description 5
- 101000831205 Danio rerio Dynein axonemal assembly factor 11 Proteins 0.000 description 4
- 102100024282 Dynein axonemal assembly factor 11 Human genes 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 241001559542 Hippocampus hippocampus Species 0.000 description 4
- 101000831210 Homo sapiens Dynein axonemal assembly factor 11 Proteins 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 230000003213 activating effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000004043 dyeing Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical group O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 230000009182 swimming Effects 0.000 description 3
- 108010026424 tau Proteins Proteins 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 2
- LHCPRYRLDOSKHK-UHFFFAOYSA-N 7-deaza-8-aza-adenine Chemical compound NC1=NC=NC2=C1C=NN2 LHCPRYRLDOSKHK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 2
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 2
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 2
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010018924 Heme Oxygenase-1 Proteins 0.000 description 2
- 102100028006 Heme oxygenase 1 Human genes 0.000 description 2
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 2
- 101000973778 Homo sapiens NAD(P)H dehydrogenase [quinone] 1 Proteins 0.000 description 2
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 description 2
- 101000686031 Homo sapiens Proto-oncogene tyrosine-protein kinase ROS Proteins 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 2
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- 108091008611 Protein Kinase B Proteins 0.000 description 2
- 102100023347 Proto-oncogene tyrosine-protein kinase ROS Human genes 0.000 description 2
- 239000009759 San-Chi Substances 0.000 description 2
- 230000003044 adaptive effect Effects 0.000 description 2
- 108010064539 amyloid beta-protein (1-42) Proteins 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960002275 pentobarbital sodium Drugs 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 229940126680 traditional chinese medicines Drugs 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 238000009966 trimming Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 230000003936 working memory Effects 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 241000721047 Danaus plexippus Species 0.000 description 1
- 206010013954 Dysphoria Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 1
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 1
- 101000617536 Homo sapiens Presenilin-1 Proteins 0.000 description 1
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- 108091036422 MiR-296 Proteins 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101000823042 Mus musculus Amyloid-beta precursor protein Proteins 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 208000031971 Yin Deficiency Diseases 0.000 description 1
- ABUBSBSOTTXVPV-UHFFFAOYSA-H [U+6].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O Chemical compound [U+6].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ABUBSBSOTTXVPV-UHFFFAOYSA-H 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 229960003135 donepezil hydrochloride Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003822 epoxy resin Substances 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000003517 fume Substances 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 102000055060 human PSEN1 Human genes 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- RLJMLMKIBZAXJO-UHFFFAOYSA-N lead nitrate Chemical compound [O-][N+](=O)O[Pb]O[N+]([O-])=O RLJMLMKIBZAXJO-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000007087 memory ability Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 108091039097 miR-193b stem-loop Proteins 0.000 description 1
- -1 micropills Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000012346 open field test Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004546 suspension concentrate Substances 0.000 description 1
- 239000007939 sustained release tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000003956 synaptic plasticity Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/77—Sapindaceae (Soapberry family), e.g. lychee or soapberry
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/898—Orchidaceae (Orchid family)
- A61K36/8988—Gastrodia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Otolaryngology (AREA)
- Anesthesiology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a traditional Chinese medicine compound, which comprises American ginseng, gastrodia elata, pseudo-ginseng, red-rooted salvia root and longan in a weight ratio of 5-8:5-8:2-4:2-4:2. The invention is used for treating dementia, dizziness, tinnitus, insomnia and the like with deficiency of qi and blood and accumulation of phlegm and blood, and mainly treats amnesia, shortness of breath, hypodynamia, slow speech, dizziness, blurred vision, tinnitus, insomnia and the like, dark purple face and lips, dark red tongue or ecchymosis, and fine and astringent pulse.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicines. More specifically, the invention relates to a traditional Chinese medicine compound and a pharmaceutical composition thereof.
Background
Rhizoma Gastrodiae, radix Panacis Quinquefolii, notoginseng radix, saviae Miltiorrhizae radix, and arillus longan are five kinds of medicinal and edible Chinese medicinal materials. Gastrodia elata suppresses liver yang, dispels external wind and dredges channels and collaterals, is an essential drug for treating dizziness and headache, and is described in Ben Cao gang mu: gastrodia elata is a wind-dispelling herb, so the gastrodia elata is a drug for dispelling wind, and is mainly used for tonifying qi and nourishing yin and promoting fluid production, and is mainly used for treating qi and yin deficiency, pseudo-ginseng activating blood and dissipating stasis, stopping bleeding and not retaining stasis, and removing stasis and not damaging the healthy energy, and is recorded in the medical Zhong Shenxi Ji: notoginseng radix, has effects of removing blood stasis, stopping bleeding, and promoting blood circulation, and can be used for treating stasis obstruction, saviae Miltiorrhizae radix with effects of promoting blood circulation, removing blood stasis, promoting tissue regeneration, clearing heart fire, cooling blood, relieving restlessness, and treating stagnation of blood stasis, dysphoria, palpitation, insomnia, longan, invigorating heart and spleen, nourishing blood, and tranquilizing mind. The study further explores the safety and effectiveness of the five-medicine compatibility prescription through experiments on the basis.
Disclosure of Invention
The invention aims to solve at least the problems and provide a traditional Chinese medicine compound and a composition thereof, which are used for treating dementia, dizziness, tinnitus, insomnia and the like caused by deficiency of qi and blood and accumulation of phlegm and blood stasis, and mainly treat amnesia, shortness of breath and weakness, slow speech, dizziness, blurred vision, tinnitus, insomnia and the like, dark purple face and lips, dark red tongue or blood stasis and fine and astringent pulse.
In order to achieve the purposes and other advantages according to the invention, a Chinese herbal compound is provided, which comprises American ginseng, gastrodia elata, pseudo-ginseng, red-rooted salvia root and longan in a weight ratio of 5-8:5-8:2-4:2-4:2.
Preferably, the American ginseng, the gastrodia tuber, the pseudo-ginseng, the red sage root and the longan are all water extracts or alcohol extracts.
Preferably, the American ginseng, the gastrodia tuber, the pseudo-ginseng, the red sage root and the longan are all raw medicines and are directly ground into powder.
Preferably, the medicine contains the Chinese herbal compound and a pharmaceutically acceptable carrier.
Preferably, the pharmaceutically acceptable carrier comprises diluents, solubilizers, cosolvents, disintegrants, dispersants, lubricants, flavoring agents, antioxidants, binders, absorbents, wetting agents, buffers, crosslinking agents.
Preferably, the medicament is formulated into a pharmaceutically acceptable dosage form.
Preferably, the dosage forms comprise pills, tablets, powders, capsules, granules, dripping pills, drops, sprays, injections, suspensions, gels and suppositories.
Preferably, the dosage form is a powder.
Preferably, the administration dosage of the traditional Chinese medicine compound in the medicine is not less than 0.4 mg/kg.d.
The invention at least comprises the following beneficial effects: gastrodia elata is a monarch drug, american is a ministerial drug, gastrodia elata eliminates evil, american ginseng is used for strengthening body resistance, pseudo-ginseng is a ministerial drug, red sage root is an adjuvant drug, and longan is a conductant drug; the five medicines are combined together, the deficiency tonifying and the blood activating are combined, the blood nourishing and the stasis removing are carried out simultaneously, the body resistance is maintained without retaining the stasis, the stasis removing and the body resistance are carried out without hurting the body resistance, and the effects of tonifying qi and nourishing blood, activating yang and resolving hard mass, and activating blood and dredging collaterals are achieved, and the five medicines are used for treating dementia, dizziness, tinnitus, insomnia and the like with the symptoms of deficiency of qi and blood and phlegm and accumulation, and mainly used for treating amnesia, shortness of breath and weakness, slow speech, dizziness, blurred vision, tinnitus, insomnia and the like, dark purple face lips, dark red tongue or blood stasis spots and thready and unsmooth pulse.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
FIG. 1 is a Y maze spontaneous alternation experiment and a new object recognition experiment before intervention;
FIG. 2 is a line graph of escape latency of mice after intervention;
FIG. 3 is a Morris water maze space exploration experiment result;
FIG. 4 is a Y maze test result;
FIG. 5 is a graph showing the results of a new object recognition experiment;
FIG. 6 shows the results of routine blood tests;
FIG. 7 shows the HE staining results for each group of mice.
Detailed Description
The present invention is described in further detail below with reference to examples to enable those skilled in the art to practice the invention by reference to the specification.
It will be understood that terms, such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
The experimental methods described in the following embodiments are conventional methods unless otherwise indicated, and the reagents and materials are commercially available.
1. Experimental materials and reagents
1.1 Experimental instrument
1.2 Experimental reagents
2 preparation of the medicament
The Chinese herbal compound is prepared from five medicines of American ginseng, gastrodia tuber, pseudo-ginseng, red sage root and longan according to the proportion of 6:6:3:3:2, and is provided by a first affiliated hospital pharmacy of Guangxi Chinese medicine university. Weighing the Chinese herbal compound, adding into physiological saline, stirring, dissolving completely, making into 80mg/mL Chinese herbal compound water solution, and placing into SB-800DTD ultrasonic cleaner (Ningbo Xinzhi biotechnology Co., ltd.) for shaking and mixing.
Donepezil hydrochloride is manufactured by the plant biotechnology Co., ltd., specification: 5 mg/tablet, approval document: chinese medicine standard character H20010723, product batch number: 22040005, preparing into 0.065mg/mL aqueous solution with physiological saline, and storing in a refrigerator at 4deg.C.
3. Experimental grouping and intervention
3.1 Grouping and marking of laboratory animals
64 SPF-class male 6 month old APP/PS1 transgenic mice (APP/PS 1 is a double transgenic mouse, expressing chimeric mouse/human amyloid precursor protein (Mo/HuAPP 695 swe) and mutant human presenilin 1 (PS 1-dE 9), both localized to CNS neurons) and 13 male APP/PS1 negative mice, supplied by Jiangsu Hua Xinnuo medical science and technology Co., ltd., laboratory animal production license number: SCXK (su) 2020-0009, experimental animal use license number: SYXK (Su) 2020-0041, quality eligibility number of experimental animals: 202245603. all experimental procedures involving animals were approved by the institutional animal welfare and ethics committee of the university of chinese medicine, guangxi, auditing lot number: DW20220707-188, all study designs and operations during the experiment conform to the 3R principles of substitution (replacement), reduction (reduction) and optimization (Refine). All mice were kept in the SPF class laboratory at the university of chinese medicine animal experiment center, guangxi, using license number: SYXK 2019-0001, animal experiment operator training accession number 22070901.
3.2 management of laboratory interventions in mice during 1 week of adaptive feeding
Humiture: and (3) reasonably ventilating according to the animal house condition, and keeping certain temperature and humidity. The temperature and humidity are set and controlled in accordance with international regulations. Temperature: (23+ -2) deg.C, the temperature is observed daily, and the temperature is adjusted as necessary. Relative humidity: 50%. Noise: 60 dB or less. Illumination: the natural environment is simulated by day and night illumination. Illumination: the lamp was turned on at 8:00 a day for 12 hours, and turned off at 20:00 a day. Ammonia gas: to keep the air fresh, it is controlled below 20 ppm. Ventilation: 15 times/hour. Airflow: 20 cm/min. Cage utensil: the SPF corncob litter in the mouse cages (beijing aogaku synergetic feed limited) was exchanged once a week. Feed: the mice were fed with a maintenance feed (Jiangsu province cooperative medical bioengineering Co., ltd.) for the nitrogen-packed C060 irradiation laboratory mice. The mice were free to ingest and drink water. The mice take food mainly at night, are filled with feed and drinking water at 15 pm every day, and check at 8 am every day to supplement feed for the feed deficiency cage. And (3) drinking water: the drinking bottle is washed every 3 days, and the fresh and clean drinking water is added in time.
3.3 grouping of mice and behavioural detection
13 APP/PS1 negative male mice served as a blank control group (Blank control group, CON), and 64 APP/PS1 male experimental mice were divided into 4 groups according to the random block method: model group (MOD), compound low dose group (Low dose group powder, LDG), compound high dose group (High dose group of powder, HDG), donepezil group (DON) hydrochloride, 16 each. The spontaneous alternation of Y maze experiment and new object identification experiment after 7 days of adaptive feeding evaluate the memory and exploratory ability of each group of mice before drug intervention.
(1) Y maze spontaneous alternation experiment (Y-maze Spontaneous Alternation Test, YSA)
The mice in each group were tested by Y maze test before and after the administration. The Y labyrinth device consists of three black opaque support arms which are 35cm long, 5cm wide and 15cm high and have an included angle of 120 degrees between the arms, and the tail ends of the three arms are stuck with different pattern marks. And a layer of padding is thinly paved at the bottom of the Y maze, and the padding is uniformly stirred and mixed before each mouse experiment so as to eliminate the interference of the walking route and smell of the previous mouse. The three arms are in turn labeled A, B, C, and the mice alternately explore three different arms (e.g., ABC, ACB, BAC, BCA, CAB, CBA) as the actual number of transitions (alternations). Non-alternating exploration of three different arms (e.g., BCB, ACA, BAB, etc.) does not account for the number of transitions. The total number of arm entries is explored minus two times as the maximum number of transitions.
The room was kept quiet during the experiment, and each mouse was placed in the Y maze for 5min before the formal experiment. After 1h interval, the formal experiment is started, mice are put into the Y maze A arm, and the head direction of each mouse is ensured to be consistent. The software monitors and records the total number of times (N) the mice entered the three arms over 5 minutes and the order of entering the arms. The mice were serially entered into 3 different arms for 1 correct alternating reaction, while the number of correct alternating reactions was recorded. Spontaneous alternation accuracy (%) =correct alternation reaction number/(total number of entries into three arms-2) ×100%. The free alternation response rate is an index for evaluating the short-term memory ability (working memory), discrimination ability of spatial position sense and orientation sense, and segment memory of the mice.
(2) New object identification experiment (Novel Object Recognition Tests, NOR)
New object identification experiment at 50X 50cm 3 The test is carried out in a black open field test box on the peripheral wall of the box, a layer of padding is thinly paved at the bottom of the box, and the padding is uniformly paved by stirring and mixing before each mouse experiment so as to eliminate the interference of the walking route and smell of the last mouse. The whole experimental process keeps the environment quiet, and avoids the factors interfering the behavior of mice as much as possible. The experimental process is divided into a training period and a detection period, and the free exploration process of the mice is observed for 5min respectively. Placing a in the object placing period 1 、a 2 Two identical objects, the detection period will be a 2 The object is changed into a b object, the mouse is placed into the box from the same position facing the box wall at the same distance from the two objects, and the camera starts to record the time and activity of the mouse for exploring the new and old objects. The time and times of the mouse contacting two objects are recorded respectively, and the mouse nose tip contacting or the distance from the recognition object is not more than 2cm, which is regarded as exploring behavior. Calculation of new object cognitive index (Object Recognition index) =t during detection period b /(T a1 +T b ) X 100%, new object cognitive index change rate = (Discrimination index) = (T) b -T a1 )/(T a1 +T b )。T b Object b (New object)Body) search time (seconds); t (T) a1 :a 1 Object (old object) explores time (seconds).
3.4 pharmaceutical intervention
The mice were tested for their behavioral manifestations by the Y maze spontaneous alternation test and new object recognition test and were given by gavage. The administration dose of the traditional Chinese medicine compound is calculated to be equivalent dose administration according to the body surface areas of clinical human and mice. 10 mL/kg.d of each mouse, uniformly weighing all the mice before each drug filling, recording and calculating the dosage of the traditional Chinese medicine of each mouse according to the number, sequentially filling the drug according to groups, and continuously filling for 4 weeks; the model group and the blank control group are subjected to gastric lavage by using an equal volume of normal saline, and index detection is carried out after continuous gastric lavage administration for 4 weeks.
(1) Blank control group: the stomach is irrigated with an equal volume of physiological saline 1 time each day;
(2) model group: the stomach is irrigated with an equal volume of physiological saline 1 time each day;
(3) compound low-dose group of traditional Chinese medicines: the traditional Chinese medicine compound gastric lavage of 0.4g/kg is administered 1 time per day;
(4) high-dose group of traditional Chinese medicine compound: the traditional Chinese medicine compound gastric lavage of 0.8g/kg is administered 1 time per day;
(5) donepezil hydrochloride group: the donepezil suspension was administered 1 gastric lavage per day at 0.65 mg/kg.
3.5 preparation of materials and samples
(1) Serum sample preparation: after the compound Chinese medicine is administrated by stomach irrigation for 4 weeks, the body weight of all experimental mice is recorded, and no water is forbidden after 12 hours of fasted before sample collection. After mice are injected into the complete anesthesia state by 50mg/kg of pentobarbital sodium with concentration of 0.3%, eyeballs take blood, whole blood stands still, serum is separated by aseptic centrifugation for 15min at 3000r/min, and the serum is stored at-80 ℃ after sub-packaging until detection.
(2) Mouse hippocampal tissue and whole brain collection and pretreatment: mice were sacrificed by cervical dislocation after blood collection by intraperitoneal injection of 50mg/kg of 0.3% pentobarbital sodium into a fully anesthetized state. The whole brain was rapidly removed on ice, and cortical tissue and hippocampus were separated and weighed. The sea horse tissue is packed with tinfoil paper and stored in a liquid nitrogen tank. Next, brain segments containing intact hippocampus were left and rapidly fixed in 4% paraformaldehyde for 24h. The fixed tissue is subjected to gradient alcohol dehydration, xylene transparency, paraffin impregnation and paraffin embedding, and a plurality of continuous coronal slices containing the largest face of the sea horse are prepared by conventional slicing, and the thickness is 5 mu m. HE staining and immunohistochemical staining were performed to observe changes in hippocampal histology.
(3) Other tissue and organ collection: after the neck-removing treatment of the mice, tissue organs such as heart, lung, liver, kidney, spleen, colon and the like are taken out, washed in physiological saline, and the filter paper is used for sucking surface moisture. Quickly immersing the tissues in 4% paraformaldehyde solution for fixation for histopathological detection, and quickly freezing the tissues which are not detected in liquid nitrogen and storing the tissues in an ultralow temperature refrigerator at-80 ℃ for later use.
(4) Mouse feces collection: on day 28 of drug intervention, mice were placed in clean metabolic cages, 1 each. After the mice relieve the bowels, the fresh faeces (more than or equal to 100 mg) of each group of mice are immediately collected by a freezing tube, the fresh faeces are collected and rapidly put into a sterile freezing tube, and are put into liquid nitrogen for quick freezing, and after 30min, the freezing tube is moved into a refrigerator at the temperature of minus 80 ℃ for preservation.
3.6 observation index and detection method
3.6.1 mouse behavioural analysis
The mouse behavioural analysis is completed in an animal behavioural room of the university of Chinese medicine science experiment center in Guangxi, the temperature of the behavioural room is 23+/-1 ℃, the illumination rhythm is 12/12 hours, and the illumination is carried out from 7 hours early to 19 hours late. The experimenter is sufficiently familiar with the mice before the start of the behavioural test and transfers the mice to the behavioural room in advance to adapt to the environment, so as to relieve the stress response brought in the test.
3.6.1.1Morris Water maze test (Morris Water Maze Tests, MWM Tests)
A circular pool with the diameter of 120cm and the height of 50cm is divided into 4 quadrants, the water depth in the pool is 26cm, and the water temperature is maintained at 23+/-1 ℃. And 1 circular platform with the diameter of 10cm and the height of 25cm is placed at the position 35cm away from the pool wall in the target quadrant, and the platform is positioned under the pool water dyed with titanium white for 1cm, so that the mice are prevented from seeing the platform. A green equilateral triangle plastic mark with a side length of 15cm is stuck on the wall of the target quadrant pool and is used as a guide for the memory and the judgment of the space position of the mice. A camera connected with a display system is arranged above the water maze, and the moving track of the mouse is synchronously recorded. And carrying out formal experiments after the adaptability training.
Positioning navigation experiment: each group of mice are placed into water from four quadrant water inlet points towards the pool wall every day, the four limbs of the mice climb up to the platform and stay for more than 10s after finding an underwater circular platform in 60s of water inlet, and the mice are recorded as escape latency; the mice were recorded for a 60s escape latency exceeding 60s and were guided to stay on the platform for 10s. After the experiment was completed, each mouse was wiped dry and the water of the mouse hair was dried using a warmer. Each mouse was tested 4 times daily for 5 consecutive days to observe the learning and memory process of the mice.
Space search experiment: and removing the circular platform on the 6 th day, putting the mouse facing the pool wall into water, and recording the path, the residence time in the original target quadrant and the times of the mouse passing through the original target platform within 60s, wherein the path, the residence time and the times are taken as detection indexes of spatial memory.
3.6.1.2Y maze spontaneous alternation experiment (Y-maze Spontaneous Alternation Test, YSA)
The method is as described above.
3.6.1.3 New object identification experiment (Novel Object Recognition Tests, NOR)
The method is as described above.
3.6.2 Paraffin-embedded sections of tissue
3.6.2.1 materials are taken: fresh tissue was fixed to 4% paraformaldehyde for more than 24h. And taking out the tissue from the fixing solution, trimming the tissue of the target part in a fume hood by using a surgical knife, and placing the trimmed tissue and a corresponding label in a dehydration box.
3.6.2.2 dehydration: and placing the dehydration box into a basket, and sequentially carrying out gradient alcohol dehydration in a dehydrator. 75% alcohol 4h-85% alcohol 2h-90% alcohol 2h-95% alcohol 1 h-absolute alcohol I30 min-absolute alcohol II 30 min-alcohol benzene 5-10 min-xylene I5-10 min-xylene II 5-10 min-wax I1 h-wax II 1 h-wax III 1h.
3.6.2.3 embedding: embedding the wax-soaked tissue in an embedding machine. Firstly, putting melted wax into an embedding frame, taking out tissues from a dehydration box before the wax is solidified, putting the tissues into the embedding frame according to the requirement of an embedding surface, and attaching corresponding labels. Cooling at-20deg.C, solidifying, removing the wax block from the embedding frame, and trimming.
3.6.2.4 slice: the trimmed wax block was placed on a paraffin microtome for slicing to a thickness of 4 μm. The slices float on warm water at 40 ℃ of a slice spreading machine to flatten the tissues, the tissues are fished up by using glass slides, and the slices are put into a 60 ℃ oven to be baked. And taking out the water after the water is baked to dry the wax and bake the wax, and preserving the wax at normal temperature for standby.
3.6.3HE dyeing
3.6.3.1 paraffin sections dewaxed to water: sequentially placing the slices into xylene I20 min-xylene II 20 min-absolute ethanol I10 min-absolute ethanol II 10min-95% alcohol 5min-90% alcohol 5min-80% alcohol 5min-70% alcohol 5 min-distilled water for washing.
3.6.3.2 hematoxylin-stained nuclei: the slices are stained with Harris hematoxylin for 3-8min, washed with tap water, differentiated with 1% hydrochloric acid alcohol for several seconds, washed with tap water, and returned to blue with 0.6% ammonia water, and washed with running water.
3.6.3.3 eosin-stained cytoplasm: the slices are dyed in eosin dye solution for 1-3min.
3.6.3.4 water-removing sealing piece: sequentially placing the slices into 95% alcohol I5 min-95% alcohol II 5 min-absolute alcohol I5 min-absolute alcohol II 5 min-xylene I5 min-xylene II 5min for dehydration and transparency, taking out the slices from the xylene, slightly airing, and sealing the slices with neutral resin.
3.6.3.5 microscopy: and (5) image acquisition and analysis.
3.6.4 Transmission Electron microscopy analysis
Taking out brain tissue, placing into 3% glutaraldehyde for fixing for 24h, washing with PBS buffer solution, fixing 2% osmium acid for 2h, dehydrating with acetone for 3 times, soaking with epoxy resin mixed solution, embedding for 24h, repairing, positioning, dyeing with toluidine blue, observing, ultrathin slicing, double dyeing with uranium acetate and lead nitrate, and observing ultrastructures such as hippocampal neurons, neuron mitochondria, and the like with a transmission electron microscope.
3.6.5 apoptosis assay
TUNEL method was used for detection. After 4 μm continuous paraffin sections in HE staining were washed 3 times with PBS buffer, the apoptosis of hippocampus, especially CA1 region, was observed with a fluorescence microscope, 10 fields per section were randomly selected for measuring apoptotic cell counts using a computer image processing system, and images were collected.
3.6.6ELISA detection
Taking 1g of mouse hippocampal tissue, adding ice physiological saline into the mouse hippocampal tissue according to the volume ratio of the mouse hippocampal tissue to the physiological saline of 1:9, and fully grinding the mixture to prepare hippocampal tissue homogenate. Centrifuging at 2500r/min for 10min at 4deg.C, collecting supernatant, and measuring Abeta 1-42, tau, and APP by ELISA method.
3.6.7real-time PCR analysis
mRNA expression of miR-193b, miR-296, abeta 1-42, tau, APP, EGFR, PI3K, akt, MAPK, ERK, FN1, HIF-1 alpha, BDNF, ROS, HO-1, NQO1 and Nrf2 was analyzed. Extracting total RNA of Hippocampus tissue by Trizol method, and analyzing RNA concentration and purity by ultraviolet spectrophotometry. The total RNA was reverse transcribed into cDNA. And designing and synthesizing related target gene primers, and then performing real-time fluorescent quantitative PCR to analyze the mRNA level of the related genes.
3.6.8Western blot analysis
Analysis of Aβ, tau, APP, MAPK, FN1, EGFR, PI3K, akt, HIF-1α, ERK, BDNF, ROS, HO-1, NQO1, nrf2 protein expression. 50mg of each group of hippocampal tissues are weighed, mixed lysate with the volume of 500 mu L is added, the hippocampal tissues are homogenized and disintegrated by adopting a tissue homogenizer, and low-temperature high-speed centrifugation (4 ℃,15000rpm,15 min) is started after the ultrasonic lysing for 30 s. Detecting protein sample concentration by using BCA kit, performing SDS-PAGE electrophoresis, western transferring, incubating the membrane with primary antibody and secondary antibody, and developing by chemiluminescence.
4 statistical method
Data were statistically processed using SPSS25.0 statistical software and plotted using GraphPad Prism 8 software. Firstly, carrying out normal and variance alignment test, and if each group meets normal distribution and the variances are aligned, adopting t test for overall mean value comparison between the two groups; the overall mean value comparison among the groups adopts One-way ANOVA (One-way ANOVA), and if the difference among the groups has statistical significance, the Bonferroni method is further adopted for carrying out the pairwise comparison. When the non-normal distribution or variance is uneven, the overall distribution between the two groups is checked by adopting a non-parameter Mann-Whitney U; the comparison between groups adopts Kruskal-Wallis test, if the difference between groups has statistical significance, the comparison is further carried out by adopting Bonferroni correction test, and P < 0.05 is the difference has statistical significance.
5 results
5.1 behavioral baseline data analysis of groups of mice prior to drug intervention
The study tested and quantified the degree of cognitive deficit in APP/PS1 mice by Y maze spontaneous alternation experiments and new object recognition experiments. The spontaneous alternation experiment of the Y maze is a behavioral test for detecting the willingness of rodents to explore new environments, the action ability and the short-time working memory ability. Rodents generally prefer to explore new areas rather than familiar areas, which are related to brain area functions such as the hippocampus, prefrontal cortex, basal forebrain, and diaphragm. The new object recognition experiment is a behavioral test for detecting the recognition memory capacity of rodents (such as mice) based on the principle that the rodents like exploring new things and generating trend behaviors, and the experiment process does not cause strong boring factors (such as water intolerance, electric shock and the like) of the mice, does not generate bad stimulus to the mice, and is more objective. New object recognition experiments can study the exploratory capacity and short-term non-spatial near memory capacity of mice, and evaluate the integrity and attention of visual object recognition memory of animals. Y maze spontaneous alternation accuracy (z= -3.267, p=0.001 < 0.05) and new object cognition index (t=3.65, p=0.00 < 0.05) were lower for APP/PS1 group mice than for CON group (fig. 1A, 1B) (×p < 0.01, ×p < 0.001, compared to CON group). APP/PS1 mice were divided into MOD group, LDG group, HDG group, DON group according to the random block method, the Y maze spontaneous alternation accuracy of 4 APP/PS1 mice was not statistically significant to the difference of the new object cognitive index total score value (f=0.040, p=0.989 > 0.05), and the Y maze spontaneous alternation accuracy of 4 APP/PS1 mice was lower than that of CON group (P < 0.05) with the new object cognitive index total score value (fig. 1C).
5.2 behavioural results in mice of groups after drug intervention
5.2.1 comparison of escape latency for Morris Water maze positioning navigation experiments
The Morris water maze positioning navigation experiment can observe the learning and memory process of the mice. The difference of escape latency of each group on day 1 of the water maze positioning navigation experiment has no statistical significance (P > 0.05); the differences for each group by day 3 were not statistically significant (h=8.241, p=0.083 > 0.05); as the mice learn in Morris water maze positioning navigation experiments, it is obvious from the comparison table (table 1) and line graph (fig. 2) of the escape latency of the mice after intervention that the escape latency of the mice in the HDG group, the LDG group, the DON group and the CON group is obviously shortened, the difference between the escape latency of the mice in the HDG group, the LDG group, the DON group and the escape latency of the mice in the CON group and the escape latency of the mice in the 5 th group (H=42.93, P=0.000 < 0.05) and the escape latency of the mice in the 5 th group (H=49.74, P=0.000 < 0.05) has statistical significance, the time for finding the platform of the mice in the HDG group, the LDG group, the DON group and the CON group is reduced compared with the time for finding the platform in the MOD group, and the difference has statistical significance (P < 0.05), and the learning of the mice in the HDG group, the LDG group, the DON group and the CON group in the Morris water maze positioning experiments is shown
TABLE 1
5.2.2Morris water maze space exploration experiment results
The MWM experiment evaluates the spatial position learning ability and memory ability of animals by forcing the experimental animals to swim, learn, memorize and search for hidden platforms in water, is related to synaptic plasticity of hippocampus and NMDA receptor function, and is a classical behavioral detection method for researching cognitive functions of animals. The experimental result of space exploration of the study shows that compared with the CON group, the MOD group mice have disordered swimming paths and no purposefulness, and have no obvious tendency of searching markers, target quadrants and target platforms; the swim paths of mice in LDG group, HDG group, and DON group were compared to MOD group, and had the purpose of finding markers, target quadrants, and platforms (fig. 3A).
The average swimming speed difference of mice in each group is statistically significant (h=47.76, p=0.00 < 0.05), the average swimming speed of mice in HDG group, LDG group, DON group, CON group is faster than that of mice in MOD group, the difference is statistically significant (P < 0.001), indicating that the motor ability of mice in MOD group is reduced compared with that of mice in CON group, and the motor ability of APP/PS1 mice is improved after the intervention of HDG group, LDG group, DON group (fig. 3B, which shows P < 0.001, compared with MOD group).
The difference in target plateau quadrant residence time was statistically significant for each group of mice (h=12.679, p=0.013 < 0.05), with the target plateau quadrant residence time for the HDG group (p=0.02 < 0.05) and the CON group (p=0.03 < 0.05) being longer than for the MOD group (fig. 3C, which represents P < 0.05 compared to the MOD group). The difference in the ratio of target platform quadrant to target platform to side quadrant time was also statistically significant for each group of mice (h=21.54, p=0.000 < 0.05). The ratio of target platform quadrant to target platform opposite quadrant time was higher for CON group (p=0.043 < 0.05), LDG group (p=0.001 < 0.05), HDG group (p=0.000 < 0.05), DON group (p=0.022 < 0.05) than for MOD group.
The difference in the number of times of crossing the original target platform was statistically significant for each group of mice (h=14.10, p=0.007 < 0.05), CON group (p=0.039 < 0.05), LDG group (p=0.011 < 0.05), DON group (p=0.033 < 0.05) more times of crossing the original target platform than MOD group, and the difference was statistically significant (fig. 3D, representing P < 0.05, compared to MOD group).
5.2.2Y maze test results
The difference in total number of movements of the three arms of the Y maze by the mice of each group was not statistically significant (f=1.943, p=0.113 > 0.05) (fig. 4A), and the difference in spontaneous alternation accuracy of the Y maze was statistically significant (h=16.38, p=0.003 < 0.05). The spontaneous alternation accuracy of the Y maze of the CON group and the HDG group was 75% and 73%, respectively, which was superior to 58% of the MOD group, and the difference was statistically significant (fig. 4B, P < 0.05, P < 0.01, compared to the MOD group).
5.2.3 New object identification experiment results
In the new object recognition experiment, MOD group mice showed reduced behavior and time for exploring new objects compared to CON group mice, and LDG group, HDG group, DON group mice showed increased behavior and time for exploring new objects (fig. 5A). The difference between the new object cognitive index and the new object cognitive index change rate of each group of mice was statistically significant (h=9.52, p=0.049 < 0.05). The new object cognitive indices of the DON group and MOD group were 68% and 47%, respectively, and the new object cognitive index change rates of the DON group and MOD group were 37% and-7%, respectively, with statistical significance of the difference (fig. 5B, which shows P < 0.05, compared to MOD group). 5.3 results of routine blood test for mice of each group after drug intervention
In order to further study the safety of the traditional Chinese medicine compound, the study detects the change condition of the blood routine detection results of mice in each group after the dry period. The results showed that the mice in each group had few cases with blood routine test results outside the normal interval. Statistical analysis shows that the mean value of various indexes of blood routine of dry prognosis is in a normal reference interval, wherein the difference of HGB test results has statistical significance (H=13.77, P=0.008 < 0.05), and further analysis shows that the HGB test results of the LDG group and the HDG group are higher than those of the CON group, and the difference has statistical significance (P=0.04 < 0.05). The differences in RBC (h=9.308, p=0.054 > 0.05), WBC (h=6.453, p=0.168 > 0.05), PLT (f=0.944, p=0.444 > 0.05) were not statistically significant for each group of mice (fig. 6, which represents P < 0.05, compared to CON group).
5.4 HE staining results of mice of each group after intervention
HE staining after drug intervention shows that CA1 neurons of sea horse areas of CON brain tissues are orderly and compact in arrangement, clear in cell outline, uniform in size, free from obvious denaturation and free from reduction in quantity. The CA1 neurons of the hippocampus of MOD group were severely damaged, the cell number was decreased, the arrangement was disordered, the cells were largely neurodegenerative, the cell bodies were concentrated and deeply stained, the shape was irregular, pathological fiber tangles were partially seen, and the number of apoptotic cells was significantly increased (shown by black arrows in fig. 7). The DON group Hippocampus CA1 region neuron structure is slightly abnormal, the nerve arrangement is neat and compact, the degeneration is occasional, and the damage degree is obviously improved compared with the MOD group as shown by black arrows. The arrangement of neurons in the CA1 region of the Hippocampus of the LDG group is relatively regular, the number of cells is not reduced, partial neurodegeneration, cell concentration and deep dyeing are realized, and the damage degree is obviously improved compared with that of a model group; the arrangement of neurons in the CA1 region of the sea horse in the HDG group is relatively regular, the cell degeneration is even, the cell body is deeply dyed, and the damage degree is obviously improved compared with that in the model group.
The traditional Chinese medicine compound comprises American ginseng, gastrodia elata, pseudo-ginseng, red-rooted salvia root and longan in a weight ratio of 5-8:5-8:2-4:2-4:2. The American ginseng, the tall gastrodia tuber, the sanchi, the red sage root and the longan are all water extracts or alcohol extracts. Or the American ginseng, the tall gastrodia tuber, the sanchi, the red sage root and the longan are all raw medicines and are directly ground into powder.
The traditional Chinese medicine compound can be directly used or used in the form of a pharmaceutical preparation.
The pharmaceutical preparation contains a therapeutically effective amount of the traditional Chinese medicine compound of the invention, and the balance is pharmaceutically acceptable carrier and excipient which are nontoxic and inert to human and animals.
The pharmaceutically acceptable carrier or excipient is one or more selected from solid, semi-solid, and liquid diluents, fillers, and pharmaceutical adjuvants. The pharmaceutical preparation of the present invention is used in the form of a unit weight dose. When the invention is used for oral administration, the composition can be prepared into tablets, sustained-release tablets, controlled-release tablets, capsules, dripping pills, micropills, suspension concentrates, emulsions, powders or granules (nano-preparations), oral liquid and the like.
The number of equipment and the scale of processing described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be readily apparent to those skilled in the art.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown, it is well suited to various fields of use, and further modifications may be readily apparent to those skilled in the art, without departing from the general concepts defined by the claims and the equivalents thereof, and therefore the invention is not limited to the specific details and illustrations shown and described herein.
Claims (8)
1. A traditional Chinese medicine composition for improving cognitive function is characterized by being prepared from American ginseng, gastrodia elata, pseudo-ginseng, red-rooted salvia root and longan in a weight ratio of 6:6:3:3:2.
2. The Chinese medicinal composition according to claim 1, wherein the American ginseng, gastrodia tuber, notoginseng, red sage root and longan are all aqueous or alcoholic extracts.
3. The Chinese medicinal composition according to claim 1, wherein the American ginseng, the gastrodia tuber, the notoginseng, the red sage root and the longan are all raw medicines and are directly ground into powder.
4. A pharmaceutical composition for improving cognitive function, which is prepared from the traditional Chinese medicine composition of claim 1 and a pharmaceutically acceptable carrier.
5. The pharmaceutical composition of claim 4, wherein the pharmaceutically acceptable carrier is selected from one or more of diluents, solubilizers, cosolvents, disintegrants, dispersants, lubricants, flavoring agents, antioxidants, binders, absorbents, wetting agents, buffers, and cross-linking agents.
6. The pharmaceutical composition of claim 4, wherein the pharmaceutical composition is formulated into a pharmaceutically acceptable dosage form.
7. The pharmaceutical composition of claim 6, wherein the dosage form is selected from the group consisting of: pills, tablets, powders, capsules, granules, drops, sprays, injections, suspensions, gels, suppositories.
8. The pharmaceutical composition of claim 6, wherein the dosage form is a powder or a drop pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211675138.2A CN116270901B (en) | 2022-12-26 | 2022-12-26 | Chinese herbal compound and pharmaceutical composition thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211675138.2A CN116270901B (en) | 2022-12-26 | 2022-12-26 | Chinese herbal compound and pharmaceutical composition thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116270901A CN116270901A (en) | 2023-06-23 |
| CN116270901B true CN116270901B (en) | 2023-11-10 |
Family
ID=86829425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211675138.2A Active CN116270901B (en) | 2022-12-26 | 2022-12-26 | Chinese herbal compound and pharmaceutical composition thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116270901B (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849979A (en) * | 2009-11-06 | 2010-10-06 | 中山市中智药业集团有限公司 | Chinese medicinal composition granules and preparation method thereof |
| CN102771791A (en) * | 2012-08-13 | 2012-11-14 | 广州白云山和记黄埔中药有限公司 | Healthcare food and preparation method and application thereof |
| CN103533948A (en) * | 2011-03-29 | 2014-01-22 | 百疗医株式会社 | Herbal compositions for treating neurological diseases and improving memory impairment |
| CN108567914A (en) * | 2018-07-25 | 2018-09-25 | 厦门元之道生物科技有限公司 | It is a kind of that there is the Chinese medicine preparation and its preparation method and application for improving sleep effect |
| CN110575500A (en) * | 2018-06-11 | 2019-12-17 | 刘代芬 | Pharmaceutical composition for cleaning blood vessel wall |
| CN114344414A (en) * | 2022-01-29 | 2022-04-15 | 甘肃朴森药业有限公司 | Traditional Chinese medicine composition for soothing nerves and helping sleep as well as preparation method and application thereof |
-
2022
- 2022-12-26 CN CN202211675138.2A patent/CN116270901B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101849979A (en) * | 2009-11-06 | 2010-10-06 | 中山市中智药业集团有限公司 | Chinese medicinal composition granules and preparation method thereof |
| CN103533948A (en) * | 2011-03-29 | 2014-01-22 | 百疗医株式会社 | Herbal compositions for treating neurological diseases and improving memory impairment |
| CN102771791A (en) * | 2012-08-13 | 2012-11-14 | 广州白云山和记黄埔中药有限公司 | Healthcare food and preparation method and application thereof |
| CN110575500A (en) * | 2018-06-11 | 2019-12-17 | 刘代芬 | Pharmaceutical composition for cleaning blood vessel wall |
| CN108567914A (en) * | 2018-07-25 | 2018-09-25 | 厦门元之道生物科技有限公司 | It is a kind of that there is the Chinese medicine preparation and its preparation method and application for improving sleep effect |
| CN114344414A (en) * | 2022-01-29 | 2022-04-15 | 甘肃朴森药业有限公司 | Traditional Chinese medicine composition for soothing nerves and helping sleep as well as preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116270901A (en) | 2023-06-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102548571A (en) | Compositions and methods for prevention and treatment of brain diseases and conditions | |
| Durán et al. | Cerebellum and spatial cognition in goldfish | |
| CN116270901B (en) | Chinese herbal compound and pharmaceutical composition thereof | |
| CN111437323A (en) | Application of vine tea extract in medicine for preventing and treating Alzheimer disease | |
| Deba et al. | An animal model to test reversal of cognitive decline associated with beta-amyloid pathologies | |
| CN102813646B (en) | Application of homomangiferin in preparing pharmaceuticals for preventing senile dementia and hypomnesis, homomangiferin pharmaceutical compositions and homomangiferin preparations | |
| CN112119977B (en) | Construction method and application of mouse model of depression and memory impairment induced by CD317 | |
| CN114869919A (en) | Application of seaweed and seaweed extract in preparation of anti-neuritis medicine and anti-neuritis medicine | |
| Sorrenti et al. | A model of systemic inflammation to study neuroinflammation | |
| CN101548987B (en) | Cell culturing extract for degrading amyloid beta, preparation method and application thereof | |
| CN107029023B (en) | Traditional Chinese medicine composition and application | |
| CN109364097A (en) | Guar gum is preparing the application in anti-depression drug and health care product | |
| CN109846950A (en) | Application of the lemon extract in the cognitive disorder drug caused by preparation prevention or treatment Alzheimer disease | |
| Kuru et al. | Electroencephalographic and behavioral effects of intracerebroventricular or intraperitoneal injections of toxic honey extract in adult Wistar rats and GAERS | |
| CN113308495B (en) | Gastrodia elata fermentation product polar component for assisting in improving memory and application thereof | |
| CN109289002B (en) | Medicinal and edible composition | |
| CN113367327B (en) | Application of ketogenic diet in preventing herpes simplex virus encephalitis | |
| CN115364164B (en) | Traditional Chinese medicine composition for treating liver depression type insomnia and application thereof | |
| CN114209717A (en) | Deer glue and its medicinal composition and use | |
| Nomso et al. | Effects of Ethanol Extract Leaves of Nymphaea lotus (water lily) on Learning and Memory in CD-1 Mice | |
| CN115813917A (en) | Compound with function of rapidly improving cognitive function and application | |
| CN114129595A (en) | Deer blood crystal and its medicinal composition and use | |
| Vijayalakshmi et al. | Anti-alzheimer activity of Citrus maxima (J. burm.) Merr fruit peel extract in mice with scopolamine induced alzheimer’s disease | |
| Barry | Rotational Behavior During the Pole Test: A Novel Behavioral Assay in a Mouse Model of Parkinson's Disease | |
| CN102772633B (en) | Medicine for treating pulmonary interstitial fibrosis, and its preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |